Resilience without resistance: gram-negative responses to antimicrobial blue light and stressors in clinical and food contexts

Antimicrobial blue light (aBL) is a promising tool for bacterial inactivation in clinical and food settings, with a low risk of resistance. This study examines cross-stress tolerance and adaptive responses of Escherichia coli following sublethal aBL exposure. We assessed the impact of aBL adaptation on bacterial sensitivity to UV-C radiation and antibiotics, as well as mutation frequency and oxidative stress tolerance. Results indicate that while aBL exposure leads to phenotypic adaptation, antibiotic susceptibility remains unaffected. aBL exposure reduced mutation frequency and increased oxidative stress tolerance, in contrast to UV treatment, which markedly increased mutagenicity. Adaptation to ampicillin or UV did not confer broad cross-protection, including against aBL. These findings suggest that aBL maintains antimicrobial efficacy without promoting resistance or co-selection and acts via a distinct photonic stress mechanism. Overall, our results support aBL as a safe and effective antimicrobial strategy for repeated use in clinical and food-related applications.